Immunomodulatory Phytochemicals in Cancer: Mechanistic Pathways and Translational Potential

Cancer development is linked to dysregulated immune surveillance, chronic inflammation, and immunosuppressive signaling within the tumor microenvironment. Emerging evidence suggests that the anticancer effects of naturally occurring phytochemicals are not directly mediated by cytotoxicity but rather by altering key components of both innate and adaptive immunity. Over the last few years, significant progress has been made in understanding the interactions of specific classes of phytochemicals, including polyphenols, flavonoids, alkaloids, and terpenoids, with immune-linked signal transduction mechanisms involved in carcinogenesis. These include the suppression of pro- and anti-inflammatory mediators, the control of immune checkpoint-related pathways, the polarization of tumor-associated macrophages, the enhancement of cytotoxic T-cell and natural killer cell functions, and the suppression of angiogenic and metastatic signaling. Notably, many phytochemicals have demonstrated translational relevance, and some have advanced to later clinical trial phases. This narrative review highlights the recent preclinical, translational, and clinical evidence on the immunomodulatory effects of phytochemicals in cancer prevention and treatment. There is an accentuated focus on mechanistic convergence, the strength of the evidence, and translational potential, and the most frequently targeted immune pathways by phytochemicals are identified, with a highlight of the major challenges of integrating them into contemporary anticancer approaches.